Abstract

Question

In patients with the chronic fatigue syndrome (CFS), what is the effectiveness of
evaluated interventions?

Data sources

Published and unpublished studies in any language were identified by searching 19
databases, including MEDLINE, EMBASE/Excerpta Medica, PsycLIT, ERIC, Current Contents,
and the Cochrane Library (to 2000). The Internet was searched using a meta-search
engine; references of retrieved articles were scanned; and individuals and organizations
were contacted through a Web site dedicated to the review and through members of 2
advisory panels.

Study selection

Studies were selected if they were randomized controlled trials (RCTs) or controlled
clinical trials of any intervention used in the treatment or management of CFS in
adults or children. Studies in which diagnoses were based on another syndrome with
criteria similar to CFS, such as those of myalgic encephalomyelitis, the chronic fatigue
immune deficiency syndrome, or chronic Epstein-Barr virus infection, were included,
but studies of fibromyalgia were not.

Main results

44 studies were included (32 studies enrolled adults, 1 enrolled children, and 2 enrolled
adults and children; 9 studies did not give age information) (n = 2801; age range 11 to 87 y, 71% women) with 31 different interventions; 36
studies were RCTs. The studies were grouped by type of intervention (behavioral, immunologic,
pharmacologic, supplements, complementary or alternative, and other interventions).
18 trials (41%) showed an overall beneficial effect of the intervention (≥ 1
clinical outcome improved). The results from the RCTs are in the Table. Cognitive
behavioral and graded exercise therapies showed beneficial effects. Overall evidence
from the other interventions was inconclusive.

Conclusions

In patients with the chronic fatigue syndrome, 31 different interventions show mixed
results for effectiveness. Cognitive behavioral therapy and graded exercise therapy
show the most promise.

Sources of funding: U.K. Policy Research Programme, Department of Health; Agency for
Healthcare Research and Quality; Veterans Evidence-Based Research, Dissemination,
and Implementation Center.

For correspondence: Ms. P. Whiting, National Health Service Centre for Reviews and
Dissemination, University of York, York, England, UK. E-mail pfw2@york.ac.uk.

Commentary

The well-done review by Whiting and colleagues does not help physicians much. In the
included studies, the treatment of CFS was done by mental health and other specialists.
Thus, as physicians, we must consider the data in terms of whether to refer. Qualified
support exists for graded exercise and cognitive behavioral therapies, but it is unknown
whether the treatment effect lasts longer than a few months, and some studies reported
high dropout rates.

The absence of a standard definition of CFS jeopardizes interpretation. Many researchers
have found so much overlap with such other syndromes as the irritable bowel syndrome
and fibromyalgia that they posit that any definition of CFS is meaningless (1, 2). They suggest we view syndromes like CFS as artifacts of specialization that obscure
the true problem of medically unexplained symptoms, which is the appropriate focus
for our research and therapeutic efforts (1, 2).

I was struck by the erratically positive results across many unrelated studies. I
suggest that the provider–patient relationship is the common feature, although it
was not reported by the authors and I have never seen it reported with controlled
interventions in these populations. However, variations in the relationship may account
for the variably positive results with so many unrelated treatments. The provider–patient
relationship, in any event, is an appropriate focus for physicians in managing patients
with CFS and can be useful in arranging referral to mental health specialists (3).

Addendum 2007

The Michigan State group has demonstrated in a RCT that primary care providers can
manage effectively patients with medically unexplained symptoms (1, 2) without increased costs (3). This can provide direction for primary care providers in managing patients with
unexaplined symptoms such as CFS.